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Caroline Svanström,1,2 Sol-Britt Lonne-Rahm,1 Klas Nordlind21Department of Dermatology, Mälarsjukhuset, Eskilstuna, Sweden; 2Department of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, SwedenCorrespondence: Caroline SvanströmDepartment of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm SE 171 76, SwedenTel +46 70 230 7268Email svanstrom.caroline@gmail.comAbstract: Psoriasis is a chronic inflammatory skin disease that may be triggered or worsened by several factors, including alcohol. A higher than average alcohol consumption is common among individuals with psoriasis. Neurobiological signaling affected by alcohol intake includes a range of neurotransmitters, such as the dopaminergic, serotonergic, and tachykinergic systems, involved in reward and drug-seeking. These neurotransmitters may also have an impact on the inflammatory processes per se in psoriasis. Future therapy may, therefore, be targeted at neurotransmitter networks involved with both alcohol intake and the inflammatory processes.Keywords: psoriasis, alcohol, pruritus, neurotransmitters

Background: Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG. Objective: To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature. Methods: Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement. Results: Twenty‐one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term 'linear prurigo' was chosen to describe this manifestation. Conclusion: Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self‐inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo. [ABSTRACT FROM AUTHOR]

Background: Various mediators have been suggested for the pathogenesis of pruritus in psoriasis. Methods: To investigate cutaneous responses of substance P in pruritic lesional and nonlesional areas of psoriasis patients and in healthy controls, substance P, saline and histamine were injected intradermally. After each injection, pruritus, flare and wheal were recorded. Results: There was no statistical difference in the latency period, duration, area under the curve and maximum intensity of pruritus evoked by substance P (10-5 and 10-6 mol/l) between psoriasis and healthy control skin. Substance P (10-5 mol/l) induced a tendency to a greater intensity of pruritus in lesional compared to nonlesional psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p < 0.05) and a lower maximum intensity of pruritus (p = 0.05) in lesional psoriasis skin than in healthy control skin. No significant difference in flare area was observed between the psoriasis patients and healthy controls. The histamine-induced wheal was smaller in psoriasis patients than in healthy individuals (p < 0.05). Conclusion: Intradermally injected substance P induced pruritus, flare and wheal in psoriasis patients. However, these responses did not differ significantly from those of the healthy controls. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction. [ABSTRACT FROM AUTHOR]

Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (++) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved. [ABSTRACT FROM AUTHOR]

The expression of heat shock protein (hsp) 65, 72 and 90 was studied in human inflamed skin after heavy metal salt treatment, by using epicutaneous patch-testing procedure and immunohistochemistry. There was a slight immunoreactivity to hsp 65 and hsp 72, but not to hsp 90 in keratinocytes in normal skin. An increased immunoreactivity to hsp 72 was obtained in apically located keratinocytes in a statistically signific ant (p<0.01) increased number of reactions to cobalt chloride and gold chloride compared to control skin. These metal salts also induced the highest degree of expression of keratinocyte intercellular adhesion molecule (ICAM)-1. There were epidermal dendritic cells as well as macrophage-like cells in the dermis, which expressed hsp 65 and hsp 90, in biopsies from metal salt-treated and control skin, while expression of hsp 72 in macrophage -like cells was found only in the dermis. [ABSTRACT FROM AUTHOR]

Host-parasite interactions and their outcome constitute a critical and challenging step in disease establishment in cutaneous leishmaniasis. In the present in vitro study we investigated the possible modulating effects of both sensory and autonomic neuropeptides that normally exist in human and mouse skin, on the uptake and leishmanicidal capacity of macrophages on Leishmania (L.) major parasites, using a monocyte/macrophage murine cell line (Raw 264.7). The sensory neuropeptides somatostatin (SOM), calcitonin gene-related peptide (CGRP) and substance P (SP) suppressed the macrophage capacity for phagocytosing L. major promastigotes at different concentrations, 10[SUP-10]10[SUP-5]M, however, the suppressive effect of SP does not reach a significant level. CGRP and SP enhanced the leishmanicidal capacity of macrophages at 10[SUP-7]M, and 10[SUP-5] M, respectively, whereas SOM was without effect. The autonomic neuropeptides vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) both suppressed the phagocytic and leishmanicidal capacities of macrophages at various concentrations, 10[SUP-10]-10[SUP-5]M. The findings indicate that neuropeptides have modulating effects on macrophage-L, major interactions. These effects might be exerted by a direct action on macrophages or indirectly through induction of other mediators. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-α) in the circulation but a reduced number of functionally intact natural IFN-α producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-α protein and IFN-α mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the non-lesional SLE biopsies we could also demonstrate IPC in 10/11 patients. In 6/11 SLE patients, IFN-α mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1/6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in non-inflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE. [ABSTRACT FROM AUTHOR]

There is increasing evidence that the nervous system has influence on the immune response. The effect of vasoactive intestinal peptide (VIP) and of serotonin and its antagonists on the challenge phase of allergic contact dermatitis in humans were tested. The substances were injected intracutaneously shortly before and 6 h after application of patch tests with nickel sulphate in nickel-allergic patients and the test areas were measured after a further 18 h. Biopsy specimens were also taken for immunohistochemistry. The diameter of the nickel sulphate-induced test reaction was significantly reduced after injection of VIP at 10-[sup 6]-10-[sup 5] mol/l, but was not affected by serotonin or ketanserin. Also tested was the influence of the substances on the response of peripheral blood mononuclear cells from nickel-allergic subjects to nickel sulphate, when added at the same time as the antigen. No effect on the cell proliferative rate was seen, except for an inhibitory effect of serotonin and its antagonists at 10-[sup 5]-10-[sup 4] mol/l. VIP, at 10-[sup 5] mol/l and serotonin at 10-[sup 4] mol/l stimulated the secretion of interferon gamma. The interleukin-2 soluble receptor secretion was slightly stimulated by 5-HT at 10-[sup 4] mol/l and by ketanserin at 10-[sup 6] mol/l. In conclusion, our results show that when injected intracutaneously in the challenge phase of allergic contact dermatitis, VIP has an inhibitory effect, which might be explained by enhanced leukocyte production of interferon gamma. [ABSTRACT FROM AUTHOR]

The value of lymphocyte reactivity in the diagnosis of hypersensitivity to amalgam restorations was studied in a group of patients with oral mucosal lesions, and in a control group. Heavy metal salts were added to lymphocyte cultures, and lymphocyte proliferation and levels of 11-2 receptors and interferon-γ (IFN-γ) were determined. After addition of mercuric chloride, a statistically significant increase of IFN-γ was seen in the patient group, indicating a higher reactivity to this metal salt. Mercuric chloride, nickel sulphate, palladium chloride and zinc chloride all stimulated lymphocyte proliferation, but there was no difference between patients and controls. Nine other metal salts tested did not influence the proliferation rate in either group. Mercuric chloride, nickel sulphate, and zinc chloride did not have any effect on the level of IL-2 receptors. Thus, certain functional tests other than crude lymphocyte proliferation may be useful in the diagnosis of amalgam hypersensitivity. [ABSTRACT FROM AUTHOR]